MODELING EFFECTS OF PH & MEMBRANE POTENTIALS ON CHARGED SOLUTES

PH 的模拟效果

• 批准号: 6280749
• 负责人: KEITH KROLL
• 金额: --
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-18 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6280749
• 关键词: bioengineering /biomedical engineering; biomedical resource; model design /development; technology /technique

The purpose of this study was to investigate the potential for estimating the change in mitochondrial proton motive force (PMF) by modeling the tracer kinetics of a lipophilic cation, Tc-99m-methoxyisobutylisonitrile (MIBI), using a multicapillary distributed model. Isolated working rat hearts were perfused with Krebs-Ringer Buffer containing Tl and MIBI under normoxic (540 Torr) (n=14) or hypoxic conditions (85 Torr) (n=6) for 30 min and then switched to a tracer free perfusate for 30 min. Timed coronary sinus (CS), interstitial fluid (ISF), and aortic perfusate samples were collected and tracer concentration determined. The ISF and CS tracer curves were fitted using a 4 region, 3 barrier blood-tissue exchange model, in order to estimate permeability-surface (PS) area products for capillary (PSc), myocyte (PSpc), and mitochondria (PSm), and volumes of distribution of the myocyte (Vpc) and mitochondrial (Vm) regions. Vm for the lipophilic cation MIBI is related to the mitochondrial membrane potential via the Nernst equation as is Vpc and the sarcolemmal membrane potential. mean + sd; * = p < 0.05 vs Tl; # = p < 0.05 vs normoxic Tracer PSc PSpc PSm Vpc Vm Normoxic Tl 3.45 + 1.05 6.76 + 6.41 1.12 + 2.53 3.92 + 1.23 3.10 + 2.56 Normoxic MIBI 0.34 + 0.23* 5.60 + 6.09 1.67 + 1.93 6.05 + 5.19 67.23 + 11.75* Hypoxic Tl 2.43 + 1.25 7.00 + 4.60 1.47 + 3.20 3.62 + 2.36 7.39 + 4.52# Hypoxic MIBI 0.22 2.94 + 2.61* 4.60 + 10.0 2.84 + 3.25 51.65 + 13.80*# +0.27* We conclude the estimated large PMF (Vm) for MIBI, relative to Tl, is consistent with reported mechanisms of MIBI uptake (lipophilic cation). The decreased Vm for MIBI during hypoxia is consistent with a decrease in PMF.

这项研究的目的是调查潜在的